The invention relates to a malleable, biodegradable hemostatic agent that can be used for mechanical sealing of bleeding bone tissue, a method for forming a malleable, biodegradable hemostatic agent of this type, and a medical implant having a coating that comprises a malleable, biodegradable hemostatic agent of this type.
Hemostasis is attained during surgeries by different procedures depending on the anatomical situation, e.g. electrocoagulation (cauterization) of the blood vessels. In a number of surgeries in the region of the skull and, predominantly, at the sternum, bone wax is used to seal the capillary vessels and thus to achieve hemostasis, because of the strong bleeding that occurs in these locations due to the anatomical situation. In the process, the bone wax is first kneaded to be soft by the surgeon and then pressed directly onto and/or into the bleeding bone areas. This blocks the flow of blood, which causes hematomas to arise and the supply vessels to ultimately become closed by fibrin.
Bone wax has been known since the 19th century and generally contains bleached bees wax and a plasticizer. Substances including almond oil, Vaseline, palmitic acid, isopropyl ester, and myristic acid isopropyl ester, can be used as plasticizer. Conventional bone waxes are viscous masses and relatively difficult to knead at room temperature. The plasticizer contained in the bees wax serves to soften the wax and make it malleable while the bone wax is being kneaded owing to the warmth of the hand. Bone waxes based on bees wax are considered to be non-degradable in the human body. Frequent components of bees wax include esters of myristic acid and higher alcohols, e.g. myristic acid myricyl ester. Presumably, the human body has no suitable enzymes for degradation of the very hydrophobic esters in a reasonable amount of time. The bone waxes that are currently commercially available have a very good hemostatic effect, but lead not infrequently to damage in the human body. See: S. E. Katz, J. Rotmann, “Adverse effects of bone wax in surgery of the orbit,” Ophthal. Plast. Reconstr., 12(2):121-126 (1996); M. Lavigne et al., “Bone-wax granuloma after femoral neck osteoplasty,” Can. J. Surg., 51(3):E58-60 (2008); R. T. Allison, “Foreign body reactions and an associated histological artifact due to bone wax,” Br. J. Biomed. Sci., 51(1):14-17 (1994); O. Eser et al., “Bone wax as a cause of foreign body reaction after lumbar disc surgery: A case report” Adv. Ther., 24(3):594-7 (2007). The very good adhesive effect on moist and also fatty bone tissue can be seen as the main advantage of conventional bone waxes.
A number of alternatives to conventional bone wax are known according to the prior art. European Patent Application Publication EP 0 109 310 A2, for example, discloses a wax-like mass that is based on calcium salts of fatty acids and oligomers of hydroxycarbonic acids.
From U.S. Pat. No. 4,595,713, German published patent application DE 32 29 540 A1, DE Utility Model 1 985 889, and European Patent Application Publication EP 1 142 597 A1 are known wax-like compositions that contain oligoesters of hydroxycarbonic acids, for example lactic acid and 6-hydroxycarbonic acid. It has been evident that acidic degradation products, which adversely affect the bone tissue due to local lowering of the pH value, are generated during hydrolytic degradation upon use of these wax-like compositions.
Compositions based on polyethers are a promising development (see U.S. Patent Application Publication Nos. US 2009/0286886 and US 2011/0002974). For example, polypropylene glycol-co-ethylene glycols) can be used as polyethers. These compositions are kneadable and spreadable when exposed to the warmth of a hand. However, the good solubility of the polyethers in aqueous media must be seen as a disadvantage. This leads to adhesion of the compositions being more difficult in the presence of strongly bleeding bone tissue due to beginning dissolution of the wax-like composition. This may possibly lead to secondary bleeding which in turn causes the seal to begin to be dissolved or be fully dissolved. However, it is a particular advantage of the mixtures that they possess no barrier function for bone healing whatsoever and are completely eliminated through the renal pathway, see A. Suwan et al., “Controversial role of two different local hemostatic agents on bone healing,” J. Am. Sci., 6(12):15-163 (2010).
Accordingly, there still is a need for a malleable, biodegradable hemostatic agent that is not associated with the disadvantages described above. The hemostatic agent should be a mass, which is kneadable and malleable at body temperature, similar to the bone wax that is commercially available thus far. The viscosity of the hemostatic agent should be high enough for the mass to withstand the pressure of bleeding. Furthermore, the hemostatic agent should have sufficient cohesion, such that it does not disintegrate or dissolve within few minutes upon contact with blood or other aqueous media. Moreover, the hemostatic agent should not release any substantial quantities of acidic or alkaline components, in order to not damage the bone tissue by a non-physiological pH. Moreover, the material should be biodegradable or it should be subject to renal elimination, such that there is no permanent barrier effect of the material that might impair the healing process of the bone tissue. In addition, the mass should not stick to rubber gloves when it is being kneaded or applied.